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In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used

In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used

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FORSCH, Kristina, Verena SCHÖNING, Greta Marie ASSMANN, Christin MOSER, Beate SIEWERT, Veronika BUTTERWECK, Jürgen DREWE, 2020. In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used. In: Phytotherapy Research. Wiley. 34(1), pp. 184-192. ISSN 0951-418X. eISSN 1099-1573. Available under: doi: 10.1002/ptr.6516

@article{Forsch2020-01vitro-49359, title={In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used}, year={2020}, doi={10.1002/ptr.6516}, number={1}, volume={34}, issn={0951-418X}, journal={Phytotherapy Research}, pages={184--192}, author={Forsch, Kristina and Schöning, Verena and Assmann, Greta Marie and Moser, Christin and Siewert, Beate and Butterweck, Veronika and Drewe, Jürgen} }

2020-01 Drewe, Jürgen Siewert, Beate Schöning, Verena Forsch, Kristina In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used Forsch, Kristina Moser, Christin Assmann, Greta Marie Drewe, Jürgen eng Moser, Christin Siewert, Beate 2020-04-30T09:27:26Z Schöning, Verena Butterweck, Veronika Ze 339, a CO<sub>2</sub> extract prepared from the leaves of Petasites hybridus, possesses antispasmodic and anti‐inflammatory effects and is proven to be effective in the treatment of allergic rhinitis. To study possible hepatotoxic effects of Ze 339, its main constituents and metabolites, a series of in vitro investigations were performed. Furthermore, different reconstituted fractions of extract (petasins and fatty acid fraction) were examined in three in vitro test systems using hepatocytes: Two human cell lines, with lower and higher activity of cytochrome P450 enzymes (HepG2, HepaRG) as well as a rodent cell line with high cytochrome P450 activity (H‐4‐II‐E), were used. Metabolic activity, assessed by the WST‐1 assay, was chosen as indicator of cytotoxicity. To assess potential bioactivation of Ze 339 compounds, metabolic experiments using S9 fractions from rats, dogs, and humans and isolated cytochromes (human/rat) were performed, and the formation of reactive metabolites was assessed by measuring cellular concentrations of glutathione and glutathione disulphide.<br /><br />Our data revealed that the cytotoxicity of Ze 339, its single constituents, and main metabolites depends on the concentration, the cytochrome activity of the cell system, and the species used. Butterweck, Veronika Attribution 4.0 International Assmann, Greta Marie 2020-04-30T09:27:26Z

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